The nervous system consists of the Central Nervous System (CNS) which consists of the brain and spinal cord and serves as the collection point of nerve impulses and the Peripheral Nervous System (PNS) which includes all of the nerves other than the brain or spinal cord and connects all parts of the body to the central nervous system. The peripheral (sensory) nervous system first receives stimuli and then the central nervous system interprets them with the peripheral (motor) nervous system initiating responses.
Neurotransmitters are chemicals that allow the movement of information from one neuron across the gap between it and the adjacent neuron. The release of neurotransmitters from one area of a neuron and the recognition of the chemicals by a receptor site on the adjacent neuron causes an electrical reaction that facilitates the release of the neurotransmitter and its movement across the gap. As such, neurotransmitters are essential for interneuronal signaling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signaling proteins. Accordingly, many illnesses and disorders result from or relate to the over- or under-production of neurotransmitters.
Acetylcholine is one example of a neurotransmitter which is particularly important in the stimulation of muscle tissue. After stimulation, acetylcholine degrades to acetate and choline, which are absorbed back into the first neuron to form another acetylcholine molecule. The poison curare blocks transmission of acetylcholine. Some nerve gases inhibit the breakdown of acetylcholine, producing a continuous stimulation of the receptor cells, and spasms of muscles such as the heart. Epinephrine (adrenaline) and norepinephrine are neurotransmitters that are secreted principally from the adrenal gland. Secretion causes an increased heart rate and the enhanced production of glucose as a ready energy source (the “fight or flight” response). In addition, another neurotransmitter, Dopamine facilitates critical brain functions and, when unusual quantities are present, abnormal dopamine neurotransmission may play a role in Parkinson's disease, certain addictions, and schizophrenia. Serotonin is another exemplary neurotransmitter which is synthesized from the amino acid tryptophan and is assumed to play a biochemical role in mood and mood disorders, including anxiety, depression, and bipolar disorder.
Neurodegenerative diseases are chronic degenerative diseases of the central nervous system that may often lead to dementia. Although the causes and mechanisms of this collection of brain diseases are not well known, they are increasing in incidence in the developed as well as the underdeveloped world and are often found in the aging population. These diseases are characterized by molecular changes in nerve cells that result in nerve cell degeneration and ultimately nerve dysfunction and cell death. Examples of neurodegenerative disease include Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, fronto-temporal dementia with Parkinson's features, progressive supranuclear palsies, essential dyskinesias, and dementia, to name a few, but there are additionally a wide variety of less common but related conditions.
Although much progress toward understanding neurodegenerative diseases has been made in recent years, few effective treatments and no cures are currently available.
In addition, the neuroimmunocutaneous system (NS) is composed of the nervous system, endocrine system, and immune system wherein each component is not distinct but rather function together as a single, integrated unit. Normal human skin expresses a variety of neuropeptides, including neuromediators and neurohormones, that are either directly derived from sensory neurons or from skin cells such as keratinocytes. Neuropeptides can be antidromically released from peripheral nerves into the skin and are implicated in the so-called neurogenic inflammation. They also exert various functions within the immune system and are thought to act as trophic substances as well as cytokines.
As such, the central and peripheral nervous system plays an influential role in the functioning of the NS. It is noted, for example, that over 80% of epidermal Langerhans cells have connections with axons of the cutaneous nerves. Autonomic connections to the enteric tract are likewise extensive. Neurons secrete a multitude of neuromediators, including vasoactive intestinal peptide, somatostatin, calcitonin gene-related peptide, substance p, neurotensin, catecholamines, endorphins and cyclic nucleotides. In addition, receptors are commonly found on cell surface membranes for serotonin, acetylcholine and other neurotransmitters. Various of these neuromediators have been shown to modulate inflammation and other properties and activities in the human skin and mucous membranes (British Journal of Dermatology, 137(6), 845-850, December 1997/L. Misery; Journal of Investigative Dermatology, 127: April 2007, Yannick Chateau, “In Vitro Reconstruction of Neuro-Epidermal Connections;” British Journal of Dermatology, 155(5), 876-882, 2006/Sancero, “Role of Neuropeptides in Psoriasis;” Archives of Dermatological Research, 259:3/January 2007/Frosch, N., “Synthesis of Prostaglandins in Psoriatic Skin.”)
Skin conditions or dermatological disorders afflict millions of people each day. These skin conditions may be acute (lasting for just a few minutes to a few hours) or chronic conditions that may plague an individual for days, months, years or even a lifetime. A multitude of different dermatological conditions exist and may be fungal, bacterial, or viral based, or may be a non-infective, immunological response such as an inflammatory response with or without an allergic component, or may be idiopathic. Accordingly, symptoms may vary and may range from mild itching, redness and swelling to severe pustules and open sores and even in certain instances may lead to debilitating manifestations such as disabling ulcerations. Regardless of the cause or particular symptoms, dermatological disorders may substantially affect the quality of an individual's life. Examples of various diseases include atopy, psoriasis, contact dermatitis, acne, cancer, vasculitis and as well as traumatic processes such as surgery, laceration, burns, and infections, each of which can adversely impact the body and its appearance.
Despite the known and demonstrable connections and interrelationships between the human nervous and muco-cutaneous, systems, little progress has been made in the treatment of wounds, scars and other diseases, disorders and traumas of the skin and mucous membranes. In general, typical treatment still relies primarily upon archaic techniques of limited utility and efficacy such as debridment, suturing and oral and topical antibiotics.
Accordingly, a new methodology is needed in the treatment of diseases, disorders and traumas of the skin and mucous membranes utilizing and exploiting the interrelationship between the nervous and muco-cutaneous systems.
While society has seen tremendous advances in the field of pharmaceuticals, there are, of course, drawbacks to the administration of any given pharmaceutical agent. Sometimes, the disadvantages, characterized as “side effects,” are so severe as to preclude administration of a particular agent at a therapeutically effective dose. In such a case, drug therapy is discontinued, and other pharmaceutical agents may be tried. Many agents in the same therapeutic class, however, display similar side effect profiles, meaning that patients either have to forego therapy or suffer from unpleasant side effects associated with a particular medication.
The pervasiveness of neurodegenerative diseases, skin wounds, scars and other diseases, disorders and traumas of the skin and mucous membranes, and their devastating impact on a patient, his/her family and society in general as well as the dearth of effective and affordable treatments compel a new and innovative approach to their treatment and remission. Accordingly, there is interest in the development of novel methods and compositions for treating such diseases and conditions. In addition, combination treatment may be employed to decrease the doses of the individual components in the resulting combinations while still preventing unwanted or harmful side effects of the individual components. Thus, there is a need to discover suitable methods for the treatment of neurodegenerative diseases, skin wounds, scars and other diseases, disorders and traumas of the skin and mucous membranes, including combination treatments and dosing strategies that result in reduction of toxicity, decreased side effects and increased therapeutic effectiveness.